title: Protein nitration impairs the myogenic tone of rat middle cerebral arteries in both ischemic and nonischemic hemispheres after ischemic stroke.
abstract: The myogenic response is crucial for maintaining vascular resistance to achieve constant perfusion during pressure fluctuations. Reduced cerebral blood flow has been reported in ischemic and nonischemic hemispheres after stroke. Ischemia-reperfusion injury and the resulting oxidative stress impair myogenic responses in the ischemic hemisphere. Yet, the mechanism by which ischemia-reperfusion affects the nonischemic side is still undetermined. The goal of the present study was to determine the effect of ischemia-reperfusion injury on the myogenic reactivity of cerebral vessels from both hemispheres and whether protein nitration due to excess peroxynitrite production is the underlying mechanism of loss of tone. Male Wistar rats were subjected to sham operation or 30-min middle cerebral artery occlusion/45-min reperfusion. Rats were administered saline, the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), or the nitration inhibitor epicatechin at reperfusion. Middle cerebral arteries isolated from another set of control rats were exposed to ex vivo oxygen-glucose deprivation with and without glycoprotein 91 tat (NADPH oxidase inhibitor) or N(ω)-nitro-l-arginine methyl ester. Myogenic tone and nitrotyrosine levels were determined. Ischemia-reperfusion injury impaired the myogenic tone of vessels in both hemispheres compared with the sham group (P < 0.001). Vessels exposed to ex vivo oxygen-glucose deprivation experienced a similar loss of myogenic tone. Inhibition of peroxynitrite parent radicals significantly improved the myogenic tone. Peroxynitrite scavenging or inhibition of nitration improved the myogenic tone of vessels from ischemic (P < 0.001 and P < 0.05, respectively) and nonischemic (P < 0.01 and P < 0.05, respectively) hemispheres. Nitration was significantly increased in both hemispheres versus the sham group and was normalized with epicatechin treatment. In conclusion, ischemia-reperfusion injury impairs vessel reactivity in both hemispheres via nitration. We suggest that sham operation rather than the nonischemic side should be used as a control in preclinical stroke studies.
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, Georgia;
authors.forename: Maha
authors.initials: M
authors.lastname: Coucha
authors.forename: Weiguo
authors.initials: W
authors.lastname: Li
authors.forename: Maribeth H
authors.initials: MH
authors.lastname: Johnson
authors.forename: Susan C
authors.initials: SC
authors.lastname: Fagan
authors.forename: Adviye
authors.initials: A
authors.lastname: Ergul
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002392:Catechin / Q000494:pharmacology; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D020521:Stroke / Q000378:metabolism* / Q000503:physiopathology
chemical_list: C466420:5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron(III) chloride; D008665:Metalloporphyrins; D002392:Catechin
keywords: contralateral hemisphere; ischemia-reperfusion injury; myogenic tone; nitration; peroxynitrite